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Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease


Year of Publication:
Contact PI Name:
Greg M. Cole
Contact PI Affiliation:
University of California Los Angeles, Departments of Medicine and Neurology, Los Angeles, California, USA
G.P. Lim, F. Yang, T. Chu, P. Chen, W. Beech, B. Teter, T. Tran, O. Ubeda, K. Hsiao Ashe, S.A. Frautschy
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Veterans Affairs Merit Reviews
Alzheimer's Association
The Elizabeth and Thomas Plott Family Foundation
Katherine and Benjamin Kagan Alzheimer's Treatment Program
Study Goal and Principal Findings:

The brain in Alzheimer’s disease (AD) shows a chronic inflammatory response characterized by activated glial cells and increased expression of cytokines and complement factors surrounding amyloid deposits. Several epidemiological studies have demonstrated a reduced risk for AD in patients using nonsteroidal anti-inflammatory drugs (NSAIDs), prompting further inquiries about how NSAIDs might influence the development of AD pathology and inflammation in the CNS. We tested the impact of chronic orally administered ibuprofen, the most commonly used NSAID, in a transgenic model of AD displaying widespread microglial activation, age-related amyloid deposits, and dystrophic neurites. These mice were created by overexpressing a variant of the amyloid precursor protein found in familial AD. Transgenepositive (Tg1) and negative (Tg2) mice began receiving chow containing 375 ppm ibuprofen at 10 months of age, when amyloid plaques first appear, and were fed continuously for 6 months. This treatment produced significant reductions in final interleukin-1b and glial fibrillary acidic protein levels, as well as a significant diminution in the ultimate number and total area of β-amyloid deposits. Reductions in amyloid deposition were supported by ELISA measurements showing significantly decreased SDS-insoluble Aβ. Ibuprofen also decreased the numbers of ubiquitin-labeled dystrophic neurites and the percentage area per plaque of antiphosphotyrosine- labeled microglia. Thus, the anti-inflammatory drug ibuprofen, which has been associated with reduced AD risk in human epidemiological studies, can significantly delay some forms of AD pathology, including amyloid deposition, when administered early in the disease course of a transgenic mouse model of AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Cyclooxygenase 1 (COX 1)
Therapeutic Target:
Cyclooxygenase 2 (COX 2)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Activated Microglia
beta Amyloid Deposits
Interleukin 6 (IL-6)
Glial Fibrillary Acidic Protein (GFAP)
Brain-Buffer Soluble beta Amyloid Peptides
Brain-Detergent Insoluble beta Amyloid Peptides
Activated Microglia
Brain-beta Amyloid Deposits
Body Weight